Prognostic Indicator Of Disease Progression Research Articles

Profound deficiencies in mature blood and bone marrow progenitor dendritic cells in Chronic Lymphocyticcytic Leukemia patients.

Chronic lymphocytic leukemia (CLL) patients are immunocompromised and highly vulnerable to serious recurrent infections. Conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs) are principal sensors of infection and are essential in orchestrating innate and adaptive immune responses to resolve infection. This study identified significant deficiencies in six functionally distinct DC subsets in blood of untreated CLL (UT-CLL) patients and selective normalization of pDCs in response to acalabrutinib (a Bruton tyrosine kinase inhibitor) therapy. DCs are continuously replenished from hematopoiesis in bone marrow (BM). Four BM developmental intermediates that give rise to cDCs and pDCs were examined and significant reductions of these were identified in UT-CLL patients supporting a precursor/progeny relationship. The deficiencies in blood DCs and BM DC progenitors were significantly associated with alterations in the Flt3/FL signaling pathway critical to DC development and function. Regarding clinical parameter, cDC subset deficiencies are associated with adverse prognostic indicators of disease progression, including IGHV mutation, CD49d, CD38, and ZAP-70 status. Importantly, UT-CLL patients with shared DC subset deficiencies had shorter time-to-first treatment (TTFT), uncovering a profound alteration in innate immunity with the potential to instruct therapeutic decision-making.

Navigating Disease Management: A Comprehensive Review of the De Ritis Ratio in Clinical Medicine.

The De Ritis ratio, defined as the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, is a widely recognized biochemical marker with significant applications in diagnosing and managing various diseases, particularly liver disorders. This comprehensive review synthesizes current knowledge surrounding the clinical relevance of the De Ritis ratio, examining its historical development, diagnostic utility, and prognostic significance across various medical conditions, including liver diseases, cardiovascular disorders, and muscular pathologies. Through an in-depth analysis of literature spanning several decades, this review highlights the role of the De Ritis ratio not only in differential diagnosis but also as a prognostic indicator for disease progression and patient outcomes. The ratio's ability to distinguish between different types of liver pathology, aid in early disease detection, and its potential use in monitoring treatment response are discussed. Additionally, the review addresses the methodological considerations, such as confounding factors and interpretation challenges, that impact the clinical utility of the De Ritis ratio. Given the evolving landscape of clinical diagnostics and the push toward more personalized medicine, the review concludes with recommendations for further research. These include longitudinal studies to explore the ratio's changes over time, comparative research across diverse populations, and technological integration to enhance diagnostic accuracy and patient care. This review aims to reaffirm the importance of the De Ritis ratio in modern clinical practice and encourages continued exploration into its potential applications and benefits in healthcare.

Tumor Growth Kinetics Based on Initial Tumor Volume Doubling Time in Active Surveillance of Low-Risk Papillary Thyroid Carcinoma.

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

Anemia as a Prognostic Marker for Disease Progression in HIV Infection

Anemia, a prevalent hematologic manifestation in individuals living with Human Immunodeficiency Virus (HIV) infection, has garnered considerable attention as a prognostic indicator for disease progression and adverse clinical outcomes. This abstract presents a comprehensive review elucidating the intricate relationship between anemia and the progression of HIV infection, incorporating epidemiological trends, underlying pathophysiological mechanisms, clinical implications, and prognostic significance. Despite advances in antiretroviral therapy (ART), anemia remains a frequent complication in HIVinfected individuals, posing substantial challenges to patient management. This paper aims to provide a nuanced understanding of anemia's role as a prognostic marker, surpassing its conventional characterization as a hematologic abnormality in the context of HIV infection. Anemia's role as a predictive marker for adverse clinical outcomes in HIV patients is explored, encompassing increased mortality rates, heightened risk of opportunistic infections, accelerated disease progression, and compromised quality of life. The review delves into its prognostic significance, shaping therapeutic decisions and prognostic assessments. This paper encapsulates the criticality of anemia as a prognostic marker for disease progression in HIV infection. Understanding its epidemiology, pathophysiological mechanisms, clinical implications, and prognostic significance is pivotal for informed clinical decision-making, prognostic assessments, and optimizing care paradigms in HIV management. Keywords: Anemia, Prognostic Marker, Disease Progression and HIV

Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Comprehensive evaluation of mitochondrial redox profile, calcium dynamics, membrane integrity and apoptosis markers in a preclinical model of severe penetrating traumatic brain injury.

Traumatic Brain Injury (TBI) is caused by the external physical assaults damages the brain. It is a heterogeneous disorder that remains a leading cause of death and disability in the military and civilian population of the United States. Preclinical investigations of mitochondrial responses in TBI have ascertained that mitochondrial dysfunction is an acute indicator of cellular damage and plays a pivotal role in long-term injury progression through cellular excitotoxicity. The current study was designed to provide an in-depth evaluation of mitochondrial endpoints with respect to redox and calcium homeostasis, and cell death responses following penetrating TBI (PTBI). To evaluate these pathological cascades, anesthetized adult male rats (N=6/group) were subjected to either 10% unilateral PTBI or Sham craniectomy. Animals were euthanized at 24h post-PTBI, and purified mitochondrial fractions were isolated from the brain injury core and perilesional areas. Overall, increased reactive oxygen and nitrogen species (ROS/RNS) production, and elevated oxidative stress markers such as 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and protein carbonyls (PC) were observed in the PTBI group compared to Sham. Mitochondrial antioxidants such as glutathione, peroxiredoxin (PRX-3), thioredoxin (TRX), nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), and catalase (CAT) levels were significantly decreased after PTBI. Likewise, PTBI mitochondria displayed significant loss of Ca2+ homeostasis, early opening of mitochondrial permeability transition pore (mPTP), and increased mitochondrial swelling. Both, outer and inner mitochondrial membrane integrity markers, such as voltage-dependent anion channels (VDAC) and cytochrome c (Cyt C) expression were significantly decreased following PTBI. The apoptotic cell death was evidenced by significantly decreased B-cell lymphoma-2 (Bcl-2) and increased glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression after PTBI. Collectively, current results highlight the comprehensive picture of mitochondria-centric acute pathophysiological responses following PTBI, which may be utilized as novel prognostic indicators of disease progression and theragnostic indicators for evaluating neuroprotection therapeutics following TBI.

SuPAR to Risk-Stratify Patients With Malaria.

Severe malaria (SM) is a leading cause of global morbidity and mortality, particularly in children in sub-Saharan Africa. However, existing malaria diagnostic tests do not reliably identify children at risk of severe and fatal outcomes. Dysregulated host immune and endothelial activation contributes to the pathogenesis of SM. Current research suggests that measuring markers of these pathways at presentation may have clinical utility as prognostic indicators of disease progression and risk of death. In this review, we focus on the available evidence implicating soluble urokinase-type plasminogen activator receptor (suPAR) as a novel and early predictor of severe and fatal malaria and discuss its potential utility for malaria triage and management.

Neutrophil lymphocyte ratio as an indicator for disease progression in Idiopathic Pulmonary Fibrosis

RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. Patients present at different stages and disease course is varied. Blood monocytes have been linked to all-cause mortality, and neutrophils...

Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis.

BackgroundDuchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM).ResultsOur search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes.ConclusionThis study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population.

How Well Do Current Laboratory Biomarkers Inform Clinical Decision-Making in Chronic Pain Management?

ObjectiveDecision-making in chronic pain patients involves a combination of subjective and objective criteria, including patient history, physical examination, imaging, and patient response to prior treatments, clinical experience, probabilities, and recognition of patterns. However, there is a distinct lack of objective laboratory biomarkers in use in routine clinical care. The objective was to review the literature to identify and describe specific biomarkers in chronic pain management.MethodsThis is a narrative review of the literature regarding the use of laboratory biomarkers in chronic pain. A librarian-assisted literature search of the PubMed, Science Direct, and Google Scholar databases was performed and resulted in 304 possible manuscripts. We included manuscripts assessing laboratory collected biomarkers from urine, serum, cerebrospinal fluid, and saliva. After screening and review of the initial literature search results, a total of 75 manuscripts were included in the narrative review.ConclusionThe studies reviewed suggested that specific biomarkers may help identify those patients at risk of disease development and function as a prognostic indicator for disease progression and treatment response. However, additional research is necessary before specific recommendations can be made, and current clinical decision-making is modified.

Early Axonal Dysfunction of the Peripheral Nervous System Influences Disease Progression of ALS: Evidence From Clinical Neuroelectrophysiology

Objective: To assess the prognostic value of the decrement in compound muscle action potential amplitude within 12 months of symptom onset (CMAP-12 amplitude) for the survival of patients with amyotrophic lateral sclerosis (ALS).Methods: Patients were stratified into 4 groups according to the decrement of the CMAP-12 amplitudes: normal (≥the lower limit of normal, LLN), mild (<LLN but ≥50% of LLN), moderate (<50% but ≥30% of LLN) and severe (<30% of LLN). All patients were followed up every 3 months. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.Results: A total of 149 patients were included in the analysis [90 males (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2% of patients, mild in 22.1%, moderate in 15.4% and severe in 38.3%. Kaplan–Meier analysis showed there was a significant difference in the overall survival across the 4 groups (p < 0.05). Further pairwise comparisons identified significant differences in survival between the normal vs. the moderate group (p < 0.05) and the normal vs. the severe group (p < 0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to that in the normal group, survival in the moderately and severely decreased groups was significantly shorter (HR 3.394, 95% CI 1.292–8.917, p = 0.013; and HR 4.732, 95% CI 2.032–11.017; p = 0.000, respectively).Conclusions: Our results suggest that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, our findings provide clinical evidence for the viewpoint that early axonal dysfunction of the peripheral nervous system accelerates disease progression of ALS.

PRO2 Disease Progression Indicators in Duchenne Muscular Dystrophy for Use in Matched Analyses Comparing Treatment Effects: A Targeted Literature Review

Duchenne muscular dystrophy (DMD) is a severe and progressive neuromuscular disease. When comparing outcomes between two populations in non-randomised studies, propensity score matching (PSM) analysis is a statistical technique used to limit bias from confounding factors. However, the choice of covariates for a PSM analysis is dependent on the outcome. Therefore, the objective of this study was to review the literature for prognostic indicators of disease progression in DMD to inform specification of PSM models of clinical outcomes as part of future non-randomised studies. MEDLINE, Embase and Cochrane Library database searches were performed up to January 2020 to identify disease progression factors in DMD. Search terms included variations of Duchenne, prognostic factors, natural history, and disease progression. Publications were assessed for relevance based on pre-specified eligibility criteria by a single reviewer with quality checks by a second. All included studies were assessed for robustness using the grading system of the Centre for Evidence-Based Medicine. The search strategy identified a total of 2,749 publications, of which 256 were included for data extraction and synthesis. Patient age (current, at onset of symptoms, and diagnosis) and glucocorticoid exposure (type, and duration) were identified as core prognostic indicators in DMD affecting a wide range of clinical outcomes, from measures of cardiac, respiratory, and bone health, to lower and upper extremity function (as quantified using e.g., the North Star Ambulatory Assessment), age at loss of independent ambulation, and fracture risk. For cardiac outcomes, identified indicators also included angiotensin-converting enzyme inhibitors, beta blockers, and diuretics. We show that patient age and glucocorticoid exposure constitute core prognostic indicators in DMD. Our synthesis should be helpful to inform specification of PSM models in this indication/disease population.

CALL Score and RAS Score as Predictive Models for Coronavirus Disease 2019.

Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease of multi-system involvement with significant pulmonary manifestations. So far, many prognostic models have been introduced to guide treatment and resource management. However, data on the impact of measurable respiratory parameters associated with the disease are scarce.Objective: To demonstrate the role of Comorbidity-Age-Lymphocyte count-Lactate dehydrogenase (CALL) score and to introduce Respiratory Assessment Scoring (RAS) model in predicting disease progression and mortality in COVID-19.Methodology: Data of 252 confirmed COVID-19 patients were collected at Pak Emirates Military Hospital (PEMH) from 10th April 2020 to 31st August 2020. The CALL score and proposed factors of RAS model, namely respiratory rate, oxygen saturation at rest, alveolar arterial gradient and minimal exercise desaturation test, were calculated on the day of admission. Progression of disease was defined and correlated with measured variables. Univariate and multivariate Cox regression analysis for each variable, its hazard ratio (HR) and 95% confidence interval (CI) were calculated, and a nomogram was made using the high-risk respiratory parameters to establish the RAS model.Results: Progression of disease and death was observed in 124 (49.2%) and 49 (19.4%) patients, respectively. Presence of more than 50% of chest infiltrates was significantly associated with worsening disease and death (p-value <0.001). Death was observed in 100% of patients who had critical disease category on presentation. Regression analysis showed that the presence of comorbidity (n: 180), in contrast to other variables of CALL score, was not a good prognosticator of disease severity (p-value: 0.565). Nonetheless, the CALL model itself was validated to be a reliable prognostic indicator of disease progression and mortality. Some 10 feet oxygen desaturation test (HR: 0.99, 95%CI: 0.95-1.04, p­-value: 0.706) was not a powerful predictor of the progression of disease. However, respiratory rate of more than 30 breaths/minute (b/m) (HR: 3.03, 95%CI: 1.77-5.19), resting oxygen saturation of less than 90% (HR: 2.41, 95%CI: 1.15-5.06), and an elevated alveolar-arterial oxygen gradient (HR: 2.14, 95%CI: 1.04-4.39) were considered statistically significant high-risk predictors of disease progression and death, in the formed RAS model. The model resulted in 85% (95%CI: 80%-89%) of area under the receiver operating characteristic curve (AUROC), with substantial positive (76%, 95%CI: 68%-83%) and negative predictive values (80%, 95%CI: 73%-87%) for a cutoff value of seven. Patients with higher CALL and RAS scores also resulted in higher mortality.Conclusion: CALL and RAS scores were strongly associated with progression and mortality in patients with COVID-19.

Brain Magnetic Spectroscopy Imaging and Hereditary Spastic Paraplegia: A Focused Systematic Review on Current Landmarks and Future Perspectives.

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to investigate in vivo brain metabolites. MRS could provide a sensitive tool for the study of hereditary spastic paraplegia (HSP) by helping to unveil the underlying biochemical mechanisms and monitoring response to treatment. This focused systematic review aimed to summarize the brain metabolite findings in studies performed in genetically determined HSP. The second aim was to provide a critical analysis and recommendations for well-designed protocols for future studies. Fourteen MRS studies have been analyzed with overall 61 HSP patients, falling within a wide range of age at onset, disease duration, and age at the MRS scan, including children and adults. The genetic diagnosis included several subtypes (SPG2/3/4/5/10/11/28/31/54). SPG11 and SPG54 have been more frequently investigated. The MRS methodology included different MR field strength, not easily comparable spectra areas varying from whole brain to various cortical areas, brain stem and cerebellum sampling. No consistency in disease severity and other outcome measures was observed. The main MRS findings corresponded to the white matter metabolite abnormalities in the corticospinal tracts. In summary, this focused review provides insights on the current knowledge of brain metabolites in HSP and, in particular, in SPG11 and SPG54. Despite the inhomogeneity of the studies to date reported, brain metabolites as assessed by MRS could represent potentially useful diagnostic markers and prognostic indicators of disease progression in HSP. Specific recommendations regarding the MRS technical protocol, CNS area sampling, study design, and applicability of findings are given.

Tumorigenic functions of serglycin: Regulatory roles in epithelial to mesenchymal transition and oncogenic signaling.

Numerous studies point out serglycin as an important regulator of tumorigenesis in a variety of malignancies. Serglycin expression correlates with the aggressive phenotype of tumor cells and serves as a poor prognostic indicator for disease progression. Although serglycin is considered as an intracellular proteoglycan, it is also secreted in the extracellular matrix by tumor cells affecting cell properties, oncogenic signaling and exosomes cargo. Serglycin directly interacts with CD44 and possibly other cell surface receptors including integrins, evoking cell adhesion and signaling. Serglycin also creates a pro-inflammatory and pro-angiogenic tumor microenvironment by regulating the secretion of proteolytic enzymes, IL-8, TGFβ2, CCL2, VEGF and HGF. Hence, serglycin activates multiple signaling cascades that drive angiogenesis, tumor cell growth, epithelial to mesenchymal transition, cancer cell stemness and metastasis. The interference with the tumorigenic functions of serglycin emerges as an attractive prospect to target malignancies.

Markers of systemic inflammation in HIV-infected patients with different HIV RNA level

Purpose: Immune reconstitution inflammatory syndrome is one of the main components of the pathogenesis of HIV infection. The severity of systemic inflammation and immune activation is an important prognostic indicator of disease progression. Aim of research: to determine the diagnostic significance of systemic inflammation markers in HIV-infected patients in depend of on the level of viral replication HIV. Methods & Materials: The study involved 224 HIV patients who were divided into three main groups according to the level of HIV replication. Patients with undetectable viremia or with a viral load (VL) less than 50 copies/ml (n = 82) were included in 1st group, with a defined patients with a level of HIV RNA concentration of more than 10 000 copies/ml (n = 74) were in 3rd group. All patients received HAART. The content of lipopolysaccharide-binding protein (LBP), procalcitonin and cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, INF-γ, INF-α) were detected in the blood serum using a solid-phase enzyme-linked immunosorbent assay. The concentration of HIV RNA (viral load of HIV, copies/ml) was determined in blood plasma by the RT-PCR. Results: Significant increase in the level of LBP and cytokines IL-1β, TNF -α, IL-6, IL-8, IL-10, INF-γ, INF-α was found in groups of patients in comparison with healthy people. An average correlation was found between the level of HIV viral load and the LBP level in the blood in the groups of patients with a defined level of HIV viremia (2nd and 3rd). In patients with HIV infection with viremia, there are signs of more active systemic inflammation, accompanied by increased production of antiendotoxin proteins and cytokines (TNF-α, IL-10, INF-α and INF-γ), compared with patients with undetectable levels of viral load of HIV. Level of procalcitonin in all groups of patients had not any statistical deviation in comparison with its level in the healthy people. Conclusion: Full suppression of HIV replication is associated with lower levels of LBP, TNF-a, IL10, INF-α and INF-γ. Antiretroviral therapy can significantly reduce the severity of systemic inflammation in patients with HIV infection, but does not ensure the normalization of the concentration of antiendotoxin proteins and cytokine status.

White matter asymmetries in patients with cerebral small vessel disease.

White matter asymmetries of the human brain have been well documented using diffusion tensor imaging. The purpose of this study was to investigate white matter asymmetry across the whole brain in cerebral small vessel disease patients and evaluate the relation between the factors which often represent disease existence and white matter asymmetry. A total of 105 nondemented elderly subjects with cerebral small vessel disease aged between 60 and 85 years were included in this study. All subjects underwent T1 MPRAGE, fluid-attenuated inversion recovery, and diffusion tensor imaging scanning. With tract-based spatial statistics in diffusion tensor imaging, this study examined the white matter asymmetries and the correlations between white matter asymmetries and four distinct factors such as deep white matter hyperintensities score, periventricular hyperintensities score, cerebral microbleed number and lacune number. The study suggested the asymmetric microstructural change in small vessel disease patients involving the right side being more injured than the left. The four factors jointly affect right brain anisotropy decrease in the middle cerebellar peduncle, the cerebral peduncle, the pontine crossing tract, the corticospinal tract, the medial lemniscus, the posterior limb of internal capsule, and the frontal pattern of white matter. Results of the study demonstrated the lost right white matter may be the main origin of dysfunction in small vessel disease patients. This asymmetry should help with the evaluation of prognostic indicators of disease progression in lesion-based neuropathology..

Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer

BackgroundWe previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer.ResultsPathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density (ρ = 0.589, p < 0.001) and MVD (ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001).ConclusionsEven if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer.Materials and MethodsAmong the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.

Clinicopathological Significance of Tumor Lymphatic Vessel Density in Head and Neck Squamous Cell Carcinoma.

Various studies have demonstrated that the lymphatic system is the additional route for solid tumor metastasis. Lymph nodes metastasis in Head and neck squamous cell carcinoma (HNSCC) is a major prognostic indicator for disease progression and a guide for therapeutic strategies. We conducted a study to compare intratumoral (IT) and peritumoral (PT) lymphatic vessel density (LVD) in HNSCC using lymphatic marker D2-40 and its correlation with lymph node metastasis, histological grading and other clinicopathological parameters. Fifty specimen of HNSCC with modified radical neck dissection tissue were included in the study group. Tissue from tumor, peritumoral tissue, tumor margin and all the lymph nodes were processed for paraffin wax blocks and histopathological diagnosis. Immunohistochemical profile of lymphatic vessels in intratumoral and peritumoral tissue was assessed by subjecting one section each from the tumor and peritumoral tissue to D2-40 immunostain. To determine LVD, four fields with the highest LVD (hot spots) were identified. The mean values were calculated by taking an average of all the measurements. The comparison of LVD between peritumoral and intratumoral area revealed significantly higher PT-LVD (P=0.001). No significant association was seen between LVD, IT-LVD and PT-LVD and different age groups, gender, site of tumor, risk factors, size of tumor, tumor inflammation, pushing/infiltrating margin and stage of tumors. Significantly higher LVD, IT-LVD and PT-LVD was seen in association with lymph node metastasis. Both high intratumoral and peritumoral LVD were found significantly associated with the presence of lymph node metastasis, however lymphatic vessels were found to be significantly more numerous and larger in peritumoral areas as compared to intratumoral lymphatics. The specificity of D2-40 as a lymphatic endothelial marker was also confirmed. The results of our study support the possibility of using the determination of tumor lymphangiogenesis to identify patients of HNSCC who are at risk of developing the lymph node metastasis.

Cryptochrome-1 Gene Expression is a Reliable Prognostic Indicator in Egyptian Patients with Chronic Lymphocytic Leukemia: A Prospective Cohort Study

ObjectiveTraditional prognostic factors have proved insufficient to account for heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining the circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL and addressed its putative role as a prognostic indicator for the clinical course of CLL.Materials and MethodsA total of 100 CLL patients at diagnosis were studied for CRY-1 gene expression by real-time reverse-transcription polymerase chain reaction and were followed for assessment of time to first treatment (TFT).Results CRY-1 was expressed in 94% of the CLL patients at diagnosis. The median CRY-1 relative gene expression level (0.006) stratified patients into high and low expression groups. Forty of 100 (40%) CLL patients showed high CRY-1, 54/100 (54%) showed low CRY-1, and 6/100 (6%) had undetectable CRY-1 gene expression. High CRY-1 gene expression was concordant with CD38+, Zap-70+, and double CD38+Zap-70+ expression; unfavorable/intermediate cytogenetics; unmutated immunoglobulin heavy-chain variable-region gene; and diffuse marrow infiltration. The high CRY-1 gene expression patient group exhibited shorter TFT than the patients with low CRY-1 gene expression. A Cox proportional hazard regression model identified CRY-1 gene expression to be independently predictive for TFT.Conclusion CRY-1 is differentially expressed among CLL patients, stratifying them into low-risk and high-risk groups. CRY-1 gene expression could constitute a reliable prognostic indicator for CLL progression, complementing the role of standard well-established prognostic factors. CRY-1 gene expression could be employed as a prognostic indicator for disease progression during the initial prognostic work-up and follow-up for CLL patients.